Gynecologic cancers remain a major problem in this country with approximately 25,000 deaths annually attributed to these diseases. The purpose of this project is to characterize the molecular genetics of this group of tumors and ultimately use that information for clinical appli- cations in designing therapeutic and prevention trials We have characterized a group of ovarian tumors which span the histologic spectrum from benign cystadenomas through tumors of "low malignant potential" (LMP) to ovarian carcinomas for mutations in the ras and p53 oncogenes. Results from this study revealed that while benign and LMP tumors possessed activated ras genes, ovarian carcinomas did not. In addition, mutations in p53 were frequent in ovarian carcinomas but not in LMP tumors. This suggests that these tumors are discrete biologic entities. We are also determining the molecular "signature" of uterine sarcomas and leiomyomas, and various endometrial specimens which span the histologic spectrum from benign to malignant. These studies will help to identify the molecular genetic events which are important in the genesis of these tumors. In addition, it will characterize the temporal relationship among these events enabling one to determine if any of these lesions can be used as markers of early disease.